OBJECTIVES: 1) To quantitate and compare the effects of digoxin on myocardial performance in heathy newborn and adult hearts. 2) To quantitate and compare the pharmacokinetics of digoxin therapy in healthy newborn and adult animals (sheep). 3) To relate digoxin serum, central nervous system, and myocardial tissue levels to toxicity in healthy newborn and adult animals (sheep). METHODS: 1) Newborn and adult sheep will be treated with high and low dose digoxin regimes. After steady state has been attained, indices of myocardial contractility and electrocardiographic variables will be measured and related to age as well as to serum and tissue digoxin levels. 2) Pharmacokinetic measurement of half life, volume of distribution, and drug clearance will be made after bolus injections and during steady state drug conditions. 3) The effects of digoxin on contractility of isolated, perfused hearts from newborn and adult animals will be studied. SIGNIFICANCE: By detailing similarities and differences in the response of newborn and adult animals to digoxin therapy, and by employing a battery of monitoring techniques to evaluate changes in myocardial contractility, the investigator hopes to gain insight into those digoxin dosage schedules which may be most appropriate for newborns and infants, the means by which digoxin's therapeutic effects are most accurately monitored, and the mechanisms of digitoxicity.